NUC-3373 in Combination With Other Agents in Patients With Advanced Solid Tumours
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT05714553|
Recruitment Status : Recruiting
First Posted : February 6, 2023
Last Update Posted : June 23, 2023
This study is an open-label, multi-arm, parallel cohort, dose validation and expansion design. The study is modular in design, allowing evaluation of the safety, efficacy and pharmacokinetics (PK) of NUC-3373 in combination with other agents for the treatment of patients with different tumour types.
Each module is designed to evaluate a different NUC-3373 combination and consists of a dose-validation phase (Phase Ib) and a dose-expansion phase (Phase II).
Phase Ib of each module will determine the safety and tolerability of the combinations for further clinical evaluation in Phase II. Approximately 6-20 evaluable patients will be enrolled in the Phase Ib stage of each module to determine safety, tolerability, and preliminary efficacy of NUC-3373 in combination with other agents. Each module will then move into Phase II to enable a further assessment of safety and efficacy in approximately 20-40 patients.
Module 1 will assess NUC-3373 + leucovorin (LV) in combination with pembrolizumab for the treatment of patients with advanced/metastatic solid tumours who have progressed on ≤2 prior therapies for metastatic disease, that may have included 1 prior immunotherapy-containing regimen (either monotherapy or in combination with chemotherapy) or who have not progressed but where addition of NUC-3373 + LV to standard pembrolizumab monotherapy may be appropriate (e.g., patients who could not tolerate post- immuno-oncology (IO) standard of care therapy).
Module 2 will assess NUC-3373 + LV in combination with docetaxel for the treatment of patients with advanced/metastatic non-small cell lung cancer (NSCLC) or pleural mesothelioma who have progressed on, or were unable to tolerate, 1 or 2 prior lines of cytotoxic chemotherapy-containing regimens for advanced/metastatic disease.
The opening of each module will be at the discretion of the Sponsor. Further modules may be added as non-clinical and clinical data become available to support additional NUC-3373 combinations and tumour types.
|Condition or disease||Intervention/treatment||Phase|
|Advanced Cancer Advanced Solid Tumor Neoplasm Malignant Metastatic Cancer Melanoma Classical Hodgkin Lymphoma Non Small Cell Lung Cancer Renal Cell Carcinoma Urothelial Carcinoma Head and Neck Squamous Cell Carcinoma Subungual Squamous Cell Carcinoma Oesophageal Carcinoma MSI-H Colorectal Cancer Gastric Cancer Triple Negative Breast Cancer Endometrial Carcinoma Pleural Mesothelioma||Drug: Fosifloxuridine Nafalbenamide Drug: Leucovorin Drug: Pembrolizumab Drug: Docetaxel||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||91 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib/II Open Label, Multi-arm, Parallel Cohort Dose Finding and Expansion Study to Assess the Safety, Pharmacokinetics and Efficacy of NUC-3373, a Nucleotide Analogue, Given in Combination With Standard Approved Agents in Patients With Advanced Solid Tumours|
|Actual Study Start Date :||March 8, 2023|
|Estimated Primary Completion Date :||August 2024|
|Estimated Study Completion Date :||January 2025|
Experimental: Module 1 (NUC-3373 + LV + pembrolizumab)
This Module is designed to evaluate the tolerability and the overall safety profile of NUC-3373 (1875 mg/m2) + LV (400 mg/m2) + pembrolizumab (200 mg) in the treatment of patients with advanced solid tumours (dose validation phase).
NUC-3373 and LV will be administered on Days 1, 8 and 15 and pembrolizumab will be administered on Day 1 of 21-day cycles. The dosing schedule may be adjusted based on emerging data with agreement from the Safety Review Committee. Following completion of the dose validation phase, expansion cohorts may be initiated at the selected dose level.
Drug: Fosifloxuridine Nafalbenamide
Other Name: Keytruda
Experimental: Module 2 (NUC-3373 + LV + docetaxel)
This Module is designed to assess NUC-3373 (750 mg/m2) + LV (400 mg/m2) + docetaxel (55 mg/m2) for the treatment of patients with advanced/metastatic NSCLC or pleural mesothelioma who have progressed on, or were unable to tolerate, 1 or 2 prior lines of cytotoxic chemotherapy-containing regimens for advanced/metastatic disease (dose validation phase).
NUC-3373 and LV will be administered on Days 1 and 22 and docetaxel will be administered on Day 8 of 28-day cycles. The dosing schedule may be adjusted based on emerging data with agreement from the Safety Review Committee. Following completion of the dose validation phase, expansion cohorts may be initiated at the selected dose level.
Drug: Fosifloxuridine Nafalbenamide
- Number of patients tolerating dose levels (maximum tolerated dose; MTD) in each of the combinations [ Time Frame: Assessed from baseline to 30 days after last dose of study drug ]MTD of NUC-3373 in each of the combinations in each patient
- Number of patients reporting treatment-emergent adverse events (TEAEs) in each of the combinations [ Time Frame: Assessed from baseline to 30 days after last dose of study drug ]TEAEs in each patient, including clinically significant laboratory changes, and changes in physical exam, vital signs and serial electrocardiograms (ECGs)
- Number of patients achieving a reduction in tumour volume (Objective response rate; ORR) [ Time Frame: Assessed from baseline to 30 days after last dose of study drug ]ORR, defined as the percentage of patients achieving a confirmed complete or partial response to treatment, based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria or immune-related RECIST criteria (iRECIST).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05714553
|Contact: NuTide:303 Project Manager||+44 (0)357 1111||NuTide303@nucana.com|
|Queen Elizabeth Hospital University Hospitals Birmingham NHS Foundation Trust||Recruiting|
|Birmingham, United Kingdom, B15 2TH|
|The Beatson West of Scotland Cancer Centre||Not yet recruiting|
|Glasgow, United Kingdom, G12 0TN|
|Guy's and St Thomas NHS Foundation Trust||Recruiting|
|London, United Kingdom, SE1 9RT|
|The Christie NHS Foundation Trust||Recruiting|
|Manchester, United Kingdom, M20 4BX|
|Study Director:||Elisabeth Oelmann, MD, PhD||NuCana plc|